Physical devices (flip of a coin, balls in an urn)
Computer generated random numbers
Avoid haphazard approaches
Avoid alternating assignment
Remember the law of large numbers
Simple randomization
Place the data in a systematic order
Add a column of random numbers
Sort the column of random numbers
Block randomization
Place the data in a systematic order
Add a column of random numbers
Sort by block and then the column of random numbers
Randomization in a cross-over design
Place the data in a systematic order
Add a column of random numbers
Sort by subject and then the column of random numbers
Random selection
Place the data in a systematic order
Add a column of random numbers
Sort by the column of random numbers
Select starting from the top
Break #2
What you have learned
How to randomize
What’s coming next
Advantages and disadvantages of randomization
Advantages of randomization
Insures covariate balance
Smoking during pregnancy and Down’s syndrome
Difficult or impossible to measure covariates
Severity of illness
Co-medications
Co-morbidities
Patient’s psychological state
Avoids selection bias
Disadvantages of randomization
Expensive
Artificial
Extra tests, extra attention
Explicit acknowledgement of uncertainty
Problems with randomized trials
Volunteer bias.
Willingness to endure painful procedures
Professional volunteers
Strong personal preferences
Birth control methods
Surgical versus non-surgical trials
Less invasive surgery
Break #3
What you have learned
Advantages and disadvantages of randomization
What’s coming next
Alternatives to randomization
When can’t you randomize, 1
Unethical
Lack of equipoise
Harmful exposures
When can’t you randomize, 2
Impractical
Too many patients
Too much time
Strong patient preferences
When can’t you randomize, 3
Impossible
Attribute variables
Retrospective studies
Some alternatives
Wait list control groups
Add on trials
Intensive versus standard advice
Randomly assign from a different end
Early stopping
Break #4
What you have learned
Alternatives to randomization
What’s coming next
Blinding
Blinding/partial blinding. Who knew what when?
Hiding information (not deception)
Not always possible (bilateral orchiectomy)
Types of blinding
Double blind
Physician and patient blinded
Single blind
Patient only
Partial blind
Evaluators blinded
Hawthorne effect
Series of studies at a GE factory.
Any change, no matter what, improved productivity
Positive response to attention.
Ascertainment bias
The tendency to self deception.
“Linus Pauling actively promoted the use of massive doses of vitamin C during the last few decades of his life. He believed it could cure just about anything from the common cold to cancer. During one interview he explained that after he and his family started taking Vitamin C supplements, they never had colds. The interviewer was a bit surprised probed a bit further ‘No colds? Ever?’ Linus Pauling responded, ‘Oh just an occasional sniffle.’”
Confusion about the placebo effect, 1
Natural course of a disease
“If a doctor treats your cold, it will go away in fourteen days. If you leave it alone, it will go away in two weeks.” Gloria Silverstein.
“The art of medicine consists in amusing the patient while nature affects the cure.” Voltaire
Confusion about the placebo effect, 2
Regression to the mean
You’re never as good as you think you are on your good days and you’re never as bad as you think you are on your bad days.